23. The relationship of interleukin, matrix metalloproteinases and gastric carcinoma infiltration length

Objective: Since on the preliminary understanding of tumor biology, people have speculated the existence of chronic inflammation associated with cancer. Gastric cancer is a serious hazard to human health and one of the most common malignant tumors. Development of gastric cancer is associated with chronic inflammation, but the relationship between tumor invasion length and chronic inflammation is unclear. Matrix metalloproteinase (matrix metalloproteinases, MMPs) is a group with Zn²⁺ and the most important protease of the degradation of extracellular matrix (extracellular matrix, ECM). MMP-2, MMP- 9 are the main MMPs family members, TIMP-1 can inhibit the vast majority of MMPs. Because of MMPs can decompose the basement membrane and extracellular matrix resulting in tumor invasion and metastasis becomes a hotspot in the research of oncology, but the relationship between the infiltrating length and MMPs is unclear. In this experiment, the length from the tumor center to microscopic tumor infiltrating edge was defined as the infiltrating length. In accordance with the infiltrating length, the specimens were divided into two groups. The aim is to observe the relationship between IL-2, IL-6, IL-10, IL-17, IL-23, MMP- 2, MMP-9, TIMP-1 and the infiltrating length of gastric cancer.
Methods: From October 2009 to March 2010, a total of 180 patients with gastric cancer were operated in gastrointestinal surgery of Affiliated Tumor Hospital of Harbin Medical University. After surgical specimens in vitro along the greater curvature or small bending opposite tumor cut open the stomach, measuring tumor size, upper and lower cutting edge of distance, taking into gastric cancer fresh tissue stored in liquid nitrogen tanks. Prototype with its tack after fixed board, we measured the length of specimens, tumor diameter, the upper and lower margin distance. Along the largest diameter of tumor, we sutured two stitches on both ends of the stomach as a marker and measured the distance between two points. And Then the specimen with board immersed in 10% formalin solution, after fixed 24 hours, we remeasured the length of gross tumor diameter, the upper and lower margin distance, marking the distance between two points. And then by the Cancer Center, we cut along the width of the maximum diameter of 0.3-0.4 cm long specimens, including the upper and lower ends of the section of the tumor and normal tissue specimens, to the tumor center as a starting point, the application of special pathology drawn knife cut each 1 cm in size of 0.3 cm × 0.3 cm full-thickness gastric wall specimens, routinely embedded in paraffin, sliced, for HE staining. According to microscopically gastric cancer infiltrating length, we divided the specimens into two groups. IL-2, IL-6, IL-10, IL-17, IL-23 cytokine mRNA and protein expression of gastric cancer samples were detected respectively by Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting (Western-blot). MMP-2, MMP-9, TIMP-1 mRNA expression of gastric cancer samples were detected by Reverse transcription polymerase chain reaction (RT-PCR).
Results: According to microscopically gastric cancer infiltrating length, we divided the specimens into two groups. Grouped as follows: Infiltration length <5 cm, a total of 97 patients; infiltration length ≥5 cm, a total of 83 cases. There were significant differences in tumor size, tumor location, gross type, depth of invasion and lymph node metastasis between the two groups. There were no significant differences in age and gender between the two groups. The expression of IL-2 mRNA and protein in the invasive length <5 cm group was significantly higher than that in the invasive length ≥5 cm group. The expression of IL-6, IL-10 mRNA and protein in the invasive length <5 cm group was significantly lower than those in the invasive length ≥5 cm group. There were no significant differences in the expression of IL- 17, IL-23 mRNA and protein between the two groups. The expression of MMP-2, MMP- 9 mRNA in the invasive length <5 cm group was significantly lower than those in the invasive length ≥5 cm group. There was no significant difference in the expression of TIMP-1 mRNA between the two groups.
Conclusions: The expression of IL-2 mRNA and protein in the invasion length <5 cm group was significantly higher than that in invasive length of ≥5 cm group. The expression of IL-6, IL-10 mRNA and protein in the invasion length <5 cm group was significantly lower ≥5 cm group. There were no significant differences in the expression of IL-17, IL-23 mRNA and protein between the two groups. The inflammatory response of the long infiltrating length of gastric cancer should be weaker than that of the short infiltrating length of gastric cancer. The expression of MMP-2, MMP-9 mRNA in the invasion length <5 cm group was significantly lower than ≥5 cm group. There was no significant difference in the expression of TIMP-1 mRNA between the two groups.